Sodium Bicarbonate → Disodium;[3,3-difluoro-1-[[2-methoxy-4-[2-oxo-3-[4-(trifluoromethoxy)phenyl]sulfanylpyrazin-1-yl]phenoxy]methyl]cyclobutyl] phosphate

Participants

Reaction Steps

To a solution of dibenzyl 3,3-difluoro-1-((2-methoxy-4-(2-oxo-3-(4-(trifluoromethoxy)phenylthio)pyrazin-1(2H)-yl)phenoxy)methyl)cyclobutyl phosphate (79 mg, 0.100 mmol) in TFA (2 mL) was stirred at RT for 3.5 hours. The mixture was concentrated. The crude product was purified by prep-HPLC (Phenomenex, Luna 5 micron 25×250 mm, flow rate=30 ml/min., gradient=20% A to 100% B in 10 min., A=90% H2O/10% MeOH/0.1% TFA, B=10% H2O/90% MeOH/0.1% TFA). Yield 46 mg, 0.075 mmol as yellow gum. The yellow gum in ACN (2 ml) was added 0.5 N aqueous sodium bicarbonate (302 μl, 0.151 mmol), the mixture was diluted with water (5 ml). The solution was then lyophilized. Yield sodium 3,3-difluoro-1-((2-methoxy-4-(2-oxo-3-(4-(trifluoromethoxy)phenylthio)pyrazin-1(2H)-yl)phenoxy)methyl)cyclobutyl phosphate (51.08 mg, 0.078 mmol, 78% yield) as off-white powder. MS (M+H=611). 1H NMR (400 MHz, MeOD) δ ppm 7.54-7.63 (2H, m), 7.19-7.33 (3 H, m), 7.02-7.17 (3H, m), 6.91 (1H, dd, J=8.44, 2.39 Hz), 4.28 (2H, s), 3.80 (3H, s), 3.13-3.32 (2H, m), 2.75-2.90 (2H, m).

Provenance & Evidence